NM_001025195.2:c.955delC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001025195.2(CES1):​c.955delC​(p.Leu319PhefsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CES1
NM_001025195.2 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
CES1 (HGNC:1863): (carboxylesterase 1) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CES1NM_001025195.2 linkc.955delC p.Leu319PhefsTer5 frameshift_variant Exon 9 of 14 ENST00000360526.8 NP_001020366.1 P23141-2
CES1NM_001025194.2 linkc.952delC p.Leu318PhefsTer5 frameshift_variant Exon 9 of 14 NP_001020365.1 P23141-1
CES1NM_001266.5 linkc.952delC p.Leu318PhefsTer5 frameshift_variant Exon 9 of 14 NP_001257.4 P23141-3
CES1XM_005255774.3 linkc.955delC p.Leu319PhefsTer5 frameshift_variant Exon 9 of 14 XP_005255831.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CES1ENST00000360526.8 linkc.955delC p.Leu319PhefsTer5 frameshift_variant Exon 9 of 14 1 NM_001025195.2 ENSP00000353720.4 P23141-2

Frequencies

GnomAD3 genomes
AF:
0.000302
AC:
46
AN:
152164
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.000962
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000225
AC:
329
AN:
1461642
Hom.:
0
Cov.:
33
AF XY:
0.000223
AC XY:
162
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00134
Gnomad4 EAS exome
AF:
0.000353
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00285
Gnomad4 NFE exome
AF:
0.0000953
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000302
AC:
46
AN:
152282
Hom.:
0
Cov.:
34
AF XY:
0.000416
AC XY:
31
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00188
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000948
Hom.:
0
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DRUG METABOLISM, ALTERED, CES1-RELATED Uncertain:1
May 17, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751662163; hg19: chr16-55846945; API